An Open-Label, Flexible-Dose Study of Retigabine Immediate Release (IR) as Adjunctive Therapy to Specified Monotherapy Antiepileptic Treatments in Adults With Partial -Onset Seizures
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 203
- Locations
- 1
- Primary Endpoint
- Number of Participants With a >=50% Reduction in Partial-onset Seizure (POS) Frequency From Baseline
Study Overview
Brief Summary
The purpose of this Phase III study is to evaluate the efficacy, safety and tolerability and health outcomes of retigabine Immediate Release (IR) as adjunctive therapy to each of the following monotherapy Antiepileptic Drug (AED) treatments: carbamazepine/oxcarbazepine, lamotrigine, levetiracetam, or valproic acid in adult subjects with partial-onset seizures (POS) using a flexible dosing regimen.
Detailed Description
This is an open-label, multi-centre, flexible dose study of retigabine immediate release (IR). The study will enroll male and female outpatients (≥ 18 years of age) with partial-onset seizures (POS) who are inadequately controlled on their current monotherapy Antiepileptic Drug (AED). Following a Screening Period of up to 2 weeks, subjects will enter an 8-week Baseline Phase to determine baseline seizure frequency. At the end of the Baseline Phase, subjects who meet or exceed the minimum seizure frequency of 4 partial seizures per 56 days, will enter the Treatment Period (4 weeks Titration, 16 weeks Flexible Dose Evaluation Phase). All subjects will receive retigabine IR starting at 150 mg/day and will be titrated to 600 mg/day by Week 4. From Week 5 onwards, subjects' doses will be maintained between 300 to 1200 mg/day using a flexible dosing regimen to optimise response and tolerability. The maximum duration of the study is approximately 33 weeks (inclusive of a 3 week Taper/Follow-up Phase).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Is 18 years of age (men or women)
- •Has a confident diagnosis of epilepsy with partial-onset seizures i.e., simple or complex partial seizures with or without secondary generalization (International League Against Epilepsy (ILAE) classification; 1981) for more than 24 weeks prior to the start of Baseline phase.
- •Has experienced at least 4 partial-onset seizures (i.e., simple or complex partial seizures with or without secondary generalization) during an 8-week (i.e., 56 days) prospective Baseline Phase with at least one partial seizure occurring during each 4 week (i.e., 28-day) period.
- •Receiving a stable dose of one of the following AEDs: carbamazepine/oxcarbazepine, lamotrigine, levetiracetam or valproic acid. The AED dose must be stable 4 weeks prior to start of collection of baseline seizure data (retrospective or prospective) and during the Baseline period.
- •Is able and willing to maintain an accurate and complete daily written seizure calendar and functional status diary or has a caregiver who is able and willing to do so for the entire duration of the study.
- •Is able to comply with dosing of study drug, background AED and all study procedures.
- •Has given written informed consent, or has a legally authorized representative who has given written informed consent, prior to the performance of any study assessments.
- •A female subject is eligible to enter and participate in the study if she is either of non-childbearing potential or child-bearing potential but has a negative pregnancy test at Screening and agrees to satisfy one of the contraception methods as listed in the protocol, and is not pregnant or lactating or planning to become pregnant during the study.
- •French subjects only: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Exclusion Criteria
- •Has a history of generalised epilepsy (e.g. Lennox-Gastaut, Juvenile Myoclonic etc.)
- •Has had status epilepticus (other than simple partial status epilepticus) within the 24 weeks prior to Baseline Visit.
- •Has participated in a previous retigabine study (subjects with documented evidence of having received placebo will be eligible).
- •Is currently or has been abusing substance(s) or other medications in the 12 months prior to Baseline visit.
- •Has taken an investigational drug, or used an investigational device, within the previous 30 days prior to screening or plans to take an investigational drug anytime during the study.
- •Is currently following or planning to follow the ketogenic diet.
- •Has been treated with vigabatrin within the past 6 months prior to collection of baseline seizure data.
- •Is planning surgery or implantation of a Vagus Nerve Stimulator (VNS) to control seizures during the study.
- •Is suffering from acute or progressive neurological disease, severe psychiatric disease, or severe mental abnormalities that are likely to interfere with the objectives of the study.
- •Has any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome.
- •Has a QTc ≥450 millisecond (msec) or greater than or equal to 480 msec for subjects with Bundle Branch Block at the time of screening.
- •Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months. Has history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt.
- •French Subjects: the French subject has participated in any study using an investigational drug during the previous 30 days or 5 half-lives (whichever is longer).
Arms & Interventions
Retigabine IR
Open Label flexible dose between 300 mg/day (minimum) and 1200 mg/day (maximum).
Intervention: Retigabine IR (Drug)
Outcomes
Primary Outcomes
Number of Participants With a >=50% Reduction in Partial-onset Seizure (POS) Frequency From Baseline
Time Frame: From Baseline through Week 20 (Day 140)/Early Withdrawal
The number of participants experiencing a \>=50% reduction from Baseline (BL) in POS frequency during the Treatment Phase (TP) (i.e., Titration Phase and Flexible Dose Evaluation \[FDE\] Phase) was measured. A POS has its onset in a limited area on one side of the brain. POSs may remain limited or may spread to involve both sides of the brain. For both the Baseline Phase and the TP, seizure frequency was calculated as a 28-day rate using the following formula: 28 x {\[(number of countable partial seizures in Phase) + (10 x number of days with innumerable seizures in Phase) + (number of occurrences of status epilepticus in Phase)\] / number of applicable days in the Phase}, where all days in the Phase are considered applicable (including days with 0 seizures), except for days on which the participant failed to complete the Seizure Diary. \>= 50% reduction from BL is calculated as 100 x (28-day partial seizure rate \[PSR\] for the TP - 28-day PSR for the BL Phase) / 28-day PSR for the BL Phase.
Secondary Outcomes
- Number of Participants With a >=25%, >=75%, or 100% Reduction in Partial-onset Seizure Frequency From Baseline(From Baseline through Week 20 (Day 140)/Early Withdrawal)
- Percent Change From Baseline in Partial-onset Seizure Frequency(From Baseline through Week 20 (Day 140)/Early Withdrawal)
- Percent Change From Baseline in Functional Status: Percentage of Days With no Missed Work or School Time(Baseline through Week 20/Early Withdrawal)
- Number of Participants With the Indicated Response for the Current Ability to do the Things You Need to do Component of the PGI-C Score(Baseline through Week 20/Early Withdrawal)
- Number of Participants With the Indicated Reduction or Increase From Baseline in Partial-onset Seizure Frequency(From Baseline through Week 20 (Day 140)/Early Withdrawal)
- Functional Status Diary (FSD): Percent Change From Baseline in Epilepsy-related Limitation of Ability to do What You Needed to(Baseline through Week 20/Early Withdrawal)
- Change From Baseline in the Short Form 36 Health Survey, Version 2 (SF-36v2) Domain Scores at Week 20/Early Withdrawal(Baseline through Week 20/Early Withdrawal)
- Change From Baseline in the SF-36v2 Physical Component Summary Score at Week 20/Early Withdrawal(Baseline through Week 20/Early Withdrawal)
- Functional Status Diary (FSD): Percent Change From Baseline in Epilepsy-related Worry(Baseline through Week 20/Early Withdrawal)
- Number of Participants With the Indicated Response for the Epilepsy-related Worry Component of the Patient Global Impression of Change (PGI-C) Score(Baseline through Week 20/Early Withdrawal)
- Functional Status Diary (FSD): Percent Change From Baseline in Epilepsy-related Limitation of Ability to do What You Wanted to(Baseline through Week 20/Early Withdrawal)
- Change From Baseline in the PGI-C Score: Epilepsy-related Worry(Baseline through Week 20/Early Withdrawal)
- Number of Participants With the Indicated Response for the Current Ability to do the Things You Want to do Component of the PGI-C Score(Baseline through Week 20/Early Withdrawal)
- Change From Baseline in the PGI-C Score: Current Ability to do the Things You Want to do(Baseline through Week 20/Early Withdrawal)
- Change From Baseline in the SF-36v2 Mental Component Summary Score at Week 20/Early Withdrawal(Baseline through Week 20/Early Withdrawal)
- Change From Baseline in the PGI-C Score: Current Ability to do the Things You Need to do(Baseline through Week 20/Early Withdrawal)